Running game key for 49ers, Seattle

(10-17) 21:16 PDT — Jim Harbaugh routinely refers to his players as “mighty men” with “superhuman” healing powers, so it wasn’t surprising that he sniffed Monday when asked if his defense was undone by a little fatigue Sunday.

In the fourth quarter of a 26-3 loss to the Giants, the 49ers allowed 91 rushing yards, more than they’d allowed in 14 of their 17 previous games. They also surrendered five rushes of at least 10 yards, one more than they’d allowed in the season’s first 23 quarters.

Were they pooped? Nope, Harbaugh said. Perhaps they lacked intensity because of the lopsided score? No telling. Asked a follow-up question on the topic, Harbaugh didn’t offer an audible reply.

Whatever the case, the 49ers’ typically mighty defense can’t afford to reprise that late-game performance when San Francisco hosts the Seahawks and running back Marshawn Lynch on Thursday.

Lynch, ranked third in the NFL in rushing (549 yards), has accounted for two of the six 100-yard performances against the 49ers in their past 59 regular-season games. In San Francisco’s 19-17 win at Seattle last year, Lynch broke the 49ers’ streak of 36 games without allowing a 100-yard rusher.

This season, Lynch’s bowling-ball style has accounted for an NFL-best 25 missed tackles, according to Pro Football Focus.

Defensive coordinator Vic Fangio said Lynch was more impressive than Philadelphia’s LeSean McCoy and Baltimore’s Ray Rice, other elite backs his unit faced in 2011.

“He’s the best back we played last year by far,” Fangio said. “He broke more tackles than any back we played against last year.”

While the defense struggled to stop the run late in Sunday’s game, the 49ers didn’t try to establish their ground game against New York.

They entered with the NFL’s leading rushing attack (195.8 yards a game) and were averaging 6.1 yards per carry, their highest mark after five games since 1954. They proceeded to call 21 first-half pass plays (19 attempts, one sack, one scramble) and nine runs against New York.

Frank Gore had eight carries – only one in the final three quarters – and Harbaugh seemed to regret the decision to stray from his team’s strength, saying, “The plan wasn’t the best plan.” Offensive coordinator Greg Roman didn’t disagree.

“Obviously, we need a better plan,” Roman said. “We need to coach the plan better, we need to execute the plan better, but Step 1 is, let’s have a better plan. That falls at my feet. I wish last week I would have done a better job of giving the players an opportunity to be successful.”

Gore has had plenty of success against the Seahawks. He has more rushing yards against Seattle (1,079 in 12 games) than any back in the league, and both of his 200-yard performances have come against the Seahawks.

As Gore noted this week, however, Seattle has become far stingier.

The Seahawks are ranked second in the NFL in rushing yards allowed (70 per game) and yards per attempt (3.3), and haven’t allowed a running back to eclipse 55 yards in six games this season. Last year, Gore averaged 71 yards and 3.2 yards a carry in two games against the Seahawks.

“I used to rip off Seattle,” Gore said, smiling.

Gore will face an imposing front seven, and Lynch will meet a similarly suffocating unit that led the NFL in run defense last year, ranks ninth this season and figures to be eager to atone for Sunday’s late-game stumble.

There might not be much room to run Thursday, but Gore and Lynch are perhaps the least likely backs to back down from the challenge, Fox analyst Howie Long said recently.

“Frank Gore and Marshawn Lynch run about as physical and as low to the ground as you can run,” Long said. “They challenge you. You will rise up to the occasion, or you will be embarrassed.”

Seahawks (4-2) at 49ers (4-2)

5:20 p.m., Channel: 7 NFL Network (810, 107.7)

Spotlight on: Outside linebacker Aldon Smith. The 49ers (nine sacks) are on pace to finish with 24 sacks, which would be their lowest total since the strike-shortened 1982 season, the same year sacks became an official NFL statistic. Defensive coordinator Vic Fangio has dismissed lack-of-pressure concerns, noting his defense ranks second in passing yards allowed (183.2). Still, Giants quarterback Eli Manning was barely touched (no sacks, one hit) Sunday, and San Francisco must do a better job disrupting Seahawks rookie Russell Wilson. Smith (team-high 4 1/2 sacks) is the most likely tormentor. In his bid for his first sack since Week 4, Smith will face Seattle left tackle Russell Okung, who hasn’t allowed a sack or QB hit this season.

Injury notes: 49ers – Receiver Mario Manningham (shoulder) is questionable but is likely to play after he finished Sunday’s game against the Giants. Left tackle Joe Staley (concussion) is questionable. Per league rules, Staley must pass a battery of tests to play. Seahawks – Pro Bowl safety Kam Chancellor (ankle) will play despite being limited in practice this week. Chancellor had season highs with 10 tackles in each of the two meetings against the 49ers in 2011.

Big Three

— Wilson (5-foot-11) slipped to the third round because of concerns about his height, but he has had only three passes batted down in 152 attempts. His 1.97 batted-down percentage is lower than 15 quarterbacks’, according to Pro Football Focus, including Alex Smith’s 2.4.

— Wilson leads the NFL with five TDs on throws traveling more than 20 yards beyond the line of scrimmage, according to ESPN. The 49ers are the only team to not allow a touchdown pass of 20-plus yards this season.

— The 49ers have rebounded from losses impressively under Jim Harbaugh. San Francisco is 4-0 after defeats and has outscored opponents 93-11 while forcing 14 turnovers in those games.